Research Article: Sarcopenia, obesity, and natural killer cell immune senescence in aging: Altered cytokine levels as a common mechanism

Date Published: August 29, 2012

Publisher: Impact Journals LLC

Author(s): Charles T. Lutz, LeBris S. Quinn.

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Abstract

Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue and declines in aging rodent models. IL-15 inhibits fat deposition and insulin resistance, is anabolic for skeletal muscle in certain situations, and is required for the development and survival of natural killer (NK) lymphocytes. We review the effect that adipokines and myokines have on NK cells, with special emphasis on IL-15. We posit that increased adipokine and decreased IL-15 levels during aging constitute a common mechanism for sarcopenia, obesity, and immune senescence.

Partial Text

An inevitable consequence of human and rodent aging is sarcopenia–loss of muscle mass [1]. Some muscle loss is due to physical inactivity, but even highly trained athletes lose muscle mass and strength with age [2-6]. Although exercise programs can prevent and/or ameliorate sarcopenia, the effectiveness of exercise interventions to build muscle and effect metabolic improvements is less efficient in elderly subjects than in the young, due to multiple cellular and biochemical changes [7, 8]. Frailty is a clinically-defined condition that includes sarcopenia and some of its consequences and is a powerful predictor of mortality [9, 10]. Adipose tissue gain also is very common in aging and is a growing health concern for all ages [11, 12]. Visceral (abdominal) fat is of the greatest health concern because it is associated with insulin resistance, type 2 diabetes, cardiovascular disease, dementia, cancer, and overall mortality [3, 13]. Although obesity can be associated with normal, increased, or decreased muscle mass, muscle weight and even muscle fiber size measurements can be misleading in aging because muscle becomes infiltrated with fat [5, 14]. Furthermore, obesity prevents muscle gain in response to functional overload, possibly through skeletal muscle mTOR hyperactivation [15, 16]. Importantly, the combination of obesity and sarcopenia (so-called sarcopenic obesity) carries high health risks [5].

 

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